Oxidant-mediated cytotoxicity

Work in several laboratories including our own has shown that polyunsaturation correlates with change in susceptibility to oxidant-mediated cytotoxicity and decreased cell survival (Wagner et al, 1993 Buettner, 1993 Wagner eta/., 1992 Spitz etal, 1992 Hart eta/., 1991 Guffyefa/., 1984). The quantitative observation on the relationship of fc/y-allylic positions and oxidizability provides a rational basis for understanding the role of polyunsaturation in oxidation-related cell death. 

SimonLM, SultropN. 1985. Lung cell oxidant injury decrease in oxidant mediated cytotoxicity by N-acetylcysteine. Eur. J. Respir. Dis. (Suppl.) 139 132-35... 

Chiang, K.T., Switzer, C.H., Akali, K.O., and Fukuto, JM. (2000). The role of oxygen and reduced oxygen species in nitric oxide-mediated cytotoxicity studies in the yeast Saccharomyces cerevisiae model system. Toxicol. Appl. Pharmacol. 167(1), 30-36. 

Simon, L.M. and Suttorp, N. (1983). Lung cell oxidant injury decrease in polymorphonuclear leucocyte mediated cytotoxicity by N-acetyl cysteine. Am. Rev. Resp. Dis. 127, 286. 

Fig. 9.3. Immunoglobulin E (IgE) and mast cell activation are important components of the mammalian response to cestode infections (ADCC, antibody dependent cell-mediated cytotoxicity Ag, antigen EO, eosinophils Feel, high affinity receptor for Fc portion of IgE LTs, leukotrienes Mac, macrophages NO, nitric oxide PGs, prostaglandins TNFa, tumour necrosis factor alpha).

Neural injury mediated by glutamate involves two important components neu-roinllammation, a neuroprotective mechanism whose prolonged presence is injurious to neurons, and oxidative stress, cytotoxic consequences produced by oxy-... 

Extracts and isolated constituents of P. sidoides were investigated for their effects on nonspecific immune functions in various bioassays 98,107,127). Results imply indirect activity, possibly through activation of macrophage functions. Activation was confirmed through the presence of tumour necrosis factor (TNF-alpha) and inorganic nitric oxides (iNOS). TNF-indncing potencies for EPs 7630 as well as interferon-like activities were also observed 128,129). Interferon (IFN)-beta prodnction increased and natural killer cell mediated cytotoxicity was enhanced in MG-63 hnman osteosarcoma cells pieincubated with Umckaloabo 130). 

Ellman, C., Corbett, J.A., Misko, T.P., McDaniel, M., and Beckerman, K.P. (1993). Nitric oxide mediates interleukin-Ip-induced cellular cytotoxicity. A potential role for nitric oxide in the ovulatory process. J. Clin. Invest. 92 3053-3056. 

Estrada, C., Gomez, C., Martin, C., Moncada, S., Gonzalez, E. (1992). Nitric oxide mediates tumor necrosis factor-alpha cytotoxicity in endothelial cells. Biochem. Biophys. Res. Commun. 186, 475-482. 

Studying the use of microspheres encapsulated with glucose oxidase (GOX) for MDR cancer treatment [115], We found that cancer cells can be extensively killed by the reactive oxidative species generated by the encapsulated GOX enzyme. The most appealing feature of this therapy is that the GOX-mediated cytotoxic effect is essentially unaffected by the MDR phenotype (Fig. 4). Further studies will be conducted to optimize this strategy. 

Nitric oxide donors and atrial natriuretic peptide have been shown to block H2O2 mediated increase in the permeability of porcine pulmonary artery endothelial cells. Erythro-9-(2-hydroxy-3-nonyl)-adenine inhibition of cyclic GMP-stimulated phosphodiesterase reduced this effect (Suttorp et al. 1996). In pig aortic endothelial cells, treatment with H2O2 (0.5 mM) for 20 h reduced the number of viable cells to 44% of control (Oberle and Schroder 1996). A 6-h preincubation with SlN-1 (0.5 mM) protected endothelial cells from H202-mediated cytotoxicity and increased viability to 81 % of control. However, SlN-1 had no protective effect when the preincubation time was reduced to 3 h or when SlN-1 and H2O2 were added simultaneously to the cells. 

Li, W.-G. Stoll, T.E., Rice, l.B. et al. (2003). Activation of NAD(P)H oxidase by hpid hydroperoxides mechanism of oxidant-mediated smooth muscle cytotoxicity. Free Radical Biology and Medicine, 134, 937-946. 

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